Post-Polio Syndrome (PPS) embodies the new neuromuscular symptoms that patients with prior paralytic poliomyelitis develop following a stable course of 20 to 40 years. It is characterized by new muscle weakness, fatigue, muscular atrophy, muscle pain, and various secondary musculoskeletal complaints. The development of new symptoms in muscles supplied by motor neurons previously affected by the poliovirus has raised fundamental questions regarding the neurobiology of the surviving motor neurons, the ongoing changes of the long standing reinnervating process, and the potential role of the poliovirus in generating a chronic immune stimulation or viral persistence. The Post-Polio Syndrome has emerged worldwide as a significant health problem causing new disability for polio survivors and has generated a series of questions for patients, treating physicians, rehabilitation facilities and other health care providers. In exchanging data from the neurological, immunological, virological, electrophysiological, and rehabilitational fields, we may gain greater insight into the pathogenesis not only of Post-Polio Syndrome but also of other motor neuron diseases such as Amyotrophic Lateral Sclerosis (ALS).